BLOOD LABILE IRON EFFECT ON NITROSATIVE STRESS DEVELOPMENT UNDER RAT EXPERIMENTAL RHABDOMYOLYSIS

I. M. Chumachenko, L. G. Kapustyanenko, S. G. Shandrenko


DOI: http://dx.doi.org/10.30970/sbi.0603.227

Abstract


Under experimental model of glycerol-induced rhabdomyolysis in rats new pool of nonheme iron formation in the blood plasma and it’s effect on NO synthesis was stu­died. On the first day after intramuscular 50% glycerol injection (10 ml/kg) more than 10 times increase of free heme content in plasma and 6 times increase of heme oxygenase activity in the liver was registered. Labile ferric iron pool formation in rhabdomyolysis rat blood plasma, which is completely absent in the samples of the intact group, was proved by EPR analysis. In period from 1st to 6th day of the experiment the contents of this form of iron was greater than 2 mg/L. It is significantly higher than the concentration of transferrin associated iron. During blood labile iron pool formation, an increase of nitrosative stress indicators was observed. On the 4th day, total NO synthase concentration in the liver, as well as S-nitrosothiols and nitrosoprolin in plasma, was 2 times higher than in control. To test the hypothesis about labile iron involvement in nitrosative stress development iron acceptor – unithiol was applied. Unithiol application led to 3 time decrease in blood plasma labile iron concentration on the 4th day of pathology in comparison with animals with experimental rhabdomyolysis. Positive correlation between blood labile iron concentration and nitrosative stress indicators was detected: total NO synthase, nitrosoprolin and S-nitrosothiols concentrations decreased by 1.5 times after blood labile iron concentration lowering. Under glycerol-stimulated rhabdomyolysis development in rat, new pool of nonheme ferric iron is formed in plasma. It is not included in transferrin and therefore is capable for chemical interactions. So we can conclude that labile iron is one of nitrosative stress initiators under rhabdomyolysis.


Keywords


iron, transferrin, rhabdomyolysis, unithiol, NO

References


1. Arnelle D.R., Bay B.J., Stamler J.S. Diethyl Dithiocarbamate-Induced Decomposition of S-Nitrosothiols. Nitric Oxide, 1997; 1(1): 56-64.
https://doi.org/10.1006/niox.1996.0107
PMid:9701045

2. Boutaud O., Jackson Roberts L. Mechanism-based therapeutic approaches to rhabdomyolysis-induced renal failure. Free Radical Biology and Medicine, 2011; 51: 1062-1067.
https://doi.org/10.1016/j.freeradbiomed.2010.10.704
PMid:21034813 PMCid:PMC3116013

3. Khan J., Brennan D.M., Bradley N. et al. 3-Nitrotyrosine in the proteins of human plasma determined by an ELISA method. Biochemical Journal, 1998; 330: 795-801
https://doi.org/10.1042/bj3300795
PMid:9480893 PMCid:PMC1219208

4. Nath K.A. Heme oxygenase-1: A provenance for cytoprotective pathways in the kidney and other tissues. Kidney International, 2006; 70: 432-443.
https://doi.org/10.1038/sj.ki.5001565
PMid:16775600

5. Nath K.A., Haggard J.J., Croatt A.J. et al. The indispensability of heme oxygenase-1 in protecting against acute heme protein-induced toxicity in vivo. American Journal of Pathology, 2000; 156: 1527-1535.
https://doi.org/10.1016/S0002-9440(10)65024-9

6. Remizova M.I., Kochetygov N.I., Gerbout K.A. et al. Effect of dinitrosyl iron complexes with glutathione on hemorrhagic shock followed by saline treatment. European Journal of Pharmacology, 2011; 662(1-3): 40-46
https://doi.org/10.1016/j.ejphar.2011.04.046
PMid:21550336

7. Sardana M.K., Sassa S., Kappas A. Hormonal regulation of heme oxygenase induction in avian hepatocyte culture. Biochemical Pharmacology, 1985; 34(16): 2937-2944.
https://doi.org/10.1016/0006-2952(85)90019-X

8. Sauret J.M., Marinides G., Wang G.K. Rhabdomyolysis. American Family Physician, 2002; 65(5): 907-912.

9. Vanin A.F., Serezhenkov V.A., Mikoyan V.D., Genkin M.V. The 2.03 signal as an indicator of dinitrosyl-iron complexes with thiol-containing ligands. Nitric Oxide, 1998; 2: 224-234.
https://doi.org/10.1006/niox.1998.0180
PMid:9851363

10. Дмитренко Н.П., Шандренко С.Г., Кузьминский С.Н. и др. Биологическая активность нового препарата - акцептора оксида азота. Журнал АМН України, 1996; 2(4): 722-731.

11. Капустяненко Л.Г., Овчаренко В.И., Дмитренко М.П. Метод определения содержания пролина,тиопролина, нитрозопролина и нитрозотиопролина в биологическом материале при помощи тонкослойной хроматографии и флуориметрии. Мат. Xго Укр. біохім. з'їзду в м. Одесі (Україна, 13-17 вересня 2010 р. Одеса), 2010; 82(4): 188.

12. Проданчук Г.Н., Шандренко С.Г., Кишко Т.О., Дмитренко Н.П. Новые аспекты механизма токсического действия гидроксиламина. Современные проблемы токсикологи, 2006; 1: 37-46.

13. Смердова Л.Н., Кишко Т.О., Паршиков А.В., Дмитренко Н.П. Изучение влияния некоторых метаболитов на синтез оксидов азота перитонеальными макрофагами крыс. Укр. биохим. журнал, 1999; 71(3): 30-34.

14. Шандренко С.Г., Кішко Т.О., Чумаченко І.М., Дмитренко М.П. Зміни в обміні оксиду азоту та заліза у щурів? спричинені азбестом. Укр. біохім. журнал, 2011; 83(2): 93-100.


Refbacks

  • There are currently no refbacks.


Copyright (c) 2012 Studia biologica

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.